Propargyl ethers of azoles



United States Patent PROPARGYL ET HERS OF AZOLES John J. DAmico,Charleston, W. Va., assignor to Monsanto Chemical Company, St. Louis,Mo., a corporation of Delaware No Drawing. Application April 18, 1955,Serial No. 502,245

19 Claims 01. 260-602) This invention relates to a new class ofcompoundsand to the method of making them. More particularly, thepresent invention relates to mixed ethers one substituent of which isderived from an azole and the other from an alkyne hydrocarbons The newcompounds contain the characteristic groupmg where R1, R2 and Rs arehydrogen or short chain alkyl groups such as methyl, ethyl, propyl,butyl and amyl and where X and Y are oxygen or sulfur. The danglingvalences on the azole ring are satisfied by hydrogen, short chain alkylradicals, short chain carboalkoxy radicals, acetyl, carboxy or residuesof carbocyclic radicals. The azolyl radicals include bi-radicals. Ageneral formula of the new compounds is [(T--Y)wCnH2n-(w+2)]z where Trepresents a radical containing the azole ring attached at the2-position to Y in which the valences of the carbon atoms in the 4- and5-position are satisfied by a member of the group consisting ofhydrogen, alkyl radicals containing less than 5 carbon atoms,carboalkoxyradicals containing less than 6 carbon atoms, acetyl andcarboxy radicals and residues of carbocyclic radicals, said carbocyclicradicals containing less than 11 carbon atoms and being selected fromthe group consisting of unsubstituted ortho-arylene, chloro substitutedortho-arylene, hydrocarbon substituted ortho-arylene, alkoxy substitutedortho-phenylene, hydroxy substituted ortho-phenylene and unsubstitutedphenenyl radicals having two of the three valences on adjacent carbonatoms, Y is selected from the group consisting of oxygen and sulfur,CnH2n-(w+2) represents a radical derived from an alkyne hydrocarbon byremoval of at least one but less than three hydrogen atoms, having thetriple bond in the beta position, w and z are integers at least 1 butless than 3 and n is an integer at least 3 but not more than 8. The newcompounds, which are termed propargyl others of azoles higher alkylhomologues thereof with the azole in aqueous solution in the form of analkali metal salt. Examples of suitable propargyl chlorides (or3-chloropropynes) are propargyl chloride, 'y-methyl-propargyl chloride(or 1- chloro-2-butyne), a,mv-trimethyl-propargyl chloride,'yethyl-propargyl chloride, 'y-propyl-propargyl chloride,butyl-propargyl chloride and 'y-amyl-propargyl chloride. While otherhalides may be employed instead of the chloride, they are moreexpensive.

The following examples are illustrative of the new comsodium hydroxidesolution and 910 grams of water. resulting solution was filtered toremove any insoluble 2,769,010 Patented Oct. so, 1956 ICC pounds and thepreparation thereof but in no manner are to be construed as limitativeof this invention.

EXAMPLE 1 2- (Z-butynylmercapto) benzothiazo le A solution of sodium 2-mercaptobenzothiazole was prepared by mixing 156 grams (0.85 mole) of2-mercaptobenzothiazole, 136 grams (0.85 mole) of 25% aqueous Theimpurities and to the filtrate there was added 73 grams (0.82 mole) of'1-chloro-2-butyne. An exothermic reaction set in immediately, thetemperature of the reaction mixture rising from 27 C. to 35 C. over aperiod of 20 minutes. The reaction mixture was stirred for approximately24 hours and the solid product separated by filtration, washed withwater until the washings were neutral to litmus and dried at 50 C. A tanpowder, M. P. 68-70" C., was obtained in 82.4% yield. Afterrecrystallization from ethyl alcohol, the melting point was 72-73" C.Analysis gave- 6.35% nitrogen and 29.57% sulfur as compared to 6.39%nitrogen and 29.24% sulfur calculated for C11H9NS2.

EXAMPLE 2 5 -ch laro-Z- 2 -propyny lmercapto benzothiazole A solution ofsodium 5-chloro-2-mercaptobenzothiazole was prepared by mixing 224 grams(1.0 mole) of 5- chloro-Z-mercaptobenzothiazole, 160 grams (1.0 mole) of25% aqueous sodium hydroxide and 1000 ml. of water. To the solution so.prepared was added and intimately mixed 107 grams (0.9'mole) ofpropargyl bromide. An exothermic reaction set in immediately thetemperature of the reaction mixture rising from 24 to 34 C. over aperiod of 5 minutes. The reaction mixture was stirred for about 5 hours,filtered, and the filter cake washed with water until the washings wereneutral to litmus. Upon drying the filter cake a tan colored solidmelting at 6466 C. was obtained in 86.5% yield. After recrystallizationfrom ethyl alcohol, the melting point was 7071"C. Analysis gave 5.97%nitrogen, 26.71% sulfur and 14.52%

chlorine as compared to 5.84% nitrogen, 26.75% sulfur A solution ofsodium 2-mercaptobenzothiazole was prepared by mixing 172 grams (1.0mole) of 97% mercaptobenzothiazole, 160 grams (1.0 mole) of 25 aqueoussodium hydroxide solution and 1000 grams or" water. The resultingsolution was filtered to remove any insolubles and to the filtrate therewas added 119 grams (1.0 mole) of propargyl bromide. An exothermicreaction set in immediately, the temperature rising from 24 to 36 C.over a period of 5 minutes. The reaction mixture was stirred for about 5hours whereupon it was extracted with 500 ml. ofdiethyl ether. The etherextract was washed with water until the washings were neutral tolitmusand dried. The ether solvent was removed in vacuo. An amber coloredoilwas obtained in 89.7% yield. Analysis gave 6.89% nitrogen and 31.38%sulfur as compared to 6.82% nitrogen and 31.24% sulfur calculated forCmHqNSz.

EXAMPLE 4 V 4 -merhyl-2- 2 -pr0pyny lmercapto) -benz0thiaz0le A solutionof sodium 4-methyl-2-mercaptobenzothiazole was prepared by mixing 101grams (0.5 mole) of 90% 4-methyl-Z-mercaptobenzothiazole, grams (0.5mole) of 25 aqueous sodium hydroxide solution and 500 grams of water..to remove any insolubles and to the filtrate there was Madded. 59.5grams (0.5 mole) of propargyl bromide.

The resulting solution was filtered An exothermic reaction set inimmediately, the temperature rising from 20 to 29 C. over a period of 5minutes. The

. reaction mixture was stirred for. about 5 hours whereupon it wasextracted with 500 ml. of diethyl. ether. The ether extract was washedwith water until the washings were neutral to litmus and dried. Theether solvent was then removed in vacuo. An amber colored oil wasobtained in 94.7% yield. Analysis gave 6.37% nitrogen as Compared to6.39% nitrogen calculated for C11H9NS2.

EXAMPLE 5 6-eth0xy-2-(Z-propynylmeroapto)-benz0thiaz0le A solution of6-ethoxy-2-mercaptobenzothiazole was prepared by mixing 82 grams (0.35mole) of 90% 6-ethoxy-2-mercaptobenzothiazole, 56 grams (0.35 mole) of25% aqueous sodium hydroxide and 500 ml. of water.

To the solution so prepared was added and intimately! mixed 41.6 grams(0.35 mole) of propargyl bromide. An exothermic reaction set inimmediately, the temperature of the reaction mixture rising from 20 to29 C. over a period of 5 minutes.

for about 5 hours, filtered, and the filter cake washed with 5:

The reaction mixture was stirred water until the washings were neutralto litmus. Upon drying the filter cake a grey colored solid melting at85- 86 C. was obtained. Analysis gave 5.66% nitrogen and 25.75% sulfuras compared to 5.62% nitrogen and 25.72% sulfur calculated forC12H11NOS2.

EXAMPLE 6 2,2 -bis- (Z-propynylmercapto) -6,6-dibenz0thiaz0le tionmixture was stirred for 20 hours, filtered, and the filter cake washedwith water until the washings were neutral to litmus. Upon drying a tancolored solid melting at 178l81 C. was obtained in a 95.8% yield. Afterrecrystallization from benzene the melting point was 184- 7 186 C.Analysis gave 6.86% nitrogen and 30.85% sulfur as compared to 6.86%nitrogen and 31.39% sulfur calculated for CzaHraNzSr.

EXAMPLE 7 4-methyl-2- (Z-propynylm ercapto thiazole A solution of sodium2-mercapto-4-methylthiazole was prepared by stirring 65.6 grams (0.5mole) of Z-mercapto-4-methylthiazole, 500 ml. of water and 80 grams (0.5mole) of 25 aqueous sodium hydroxide for about minutes. The solution wasfiltered to remove any impurities and to the \clear stirred filtratethere was added 59.5 grams (0.5 mole) of propargyl bromide. Anexothermic reaction set in, the temperature rising from 24 to 35 C. overa period of about 5 minutes. The reaction mixture was stirred for about5 hours, 500 ml. of ethyl ether was added and the stirring continued for15 minutes. The ether solution was washed with water until the washingswere neutral to litmus and dried over sodium sulfate. obtained as theresidue in 91.4% yield was an amber oil. Analysis gave 8.36% nitrogenand 38.09% sulfur as compared to 8.27% nitrogen and 37.88% sulfurcalculated for C'ZH'INS2.

EXAMPLE 8 Ethyl, 4-methyl-2- (2-pr0pynylmercapt0) -5-thiaz0lecarboxylate A solution of S-carbethoxy-4-methyl-2-thiazolethiol The ether wasremoved in vacuo. The product 1 by mixing 50.8 grams (0.25 mole) of5-carbethoxy-4- methyl-2-thiazolethiol, 250 grams of water and 40 grams(0.25 mole) of 25% aqueous sodium hydroxide, To the solution so preparedwas added and intimately mixed 29.8 grams (0.25 mole) of propargylbromide. An exothermic reaction set in immediately, the temperature ofthe reaction mixture rising from 27 to 36 C. in about 5 minutes. Thereaction mixture was stirred for about 5 hours, filtered and the filtercake washed with Water until the washings were neutral to litmus. Upondrying the filter cake a tan [colored solid, M. P. 46-49 C., wasobtained in 98% yield. After recrystallization from dilute ethyl alcoholthe melting point was 50-51 C. Analysis gave 6.12% nitrogen and 26.69%sulfur as compared to 5.80% nitrogen and 26.57% sulfur calculated forCwHuNOzSz.

EXAMPLE 9 Methyl, 4-meZhyl-2-(Z-propynylmercapto) -5-thiaz0lecarboxylateA solution of 5-carbomethoxy-4-methyl-2-thiazolethiol was prepared bymixing 48.3 grams (0.25 mole) of5-.carbometl1oxy-4-methyl-2-thiazolethiol, 250 grams of water and 40grams (0.25 mole) of 25% aqueous sodium hydroxide. To the solution soprepared was added and intimately mixed 29.8 grams (0.25 mole) ofpropargyl bromide. An exothermic reaction set in immediately, thetemperature of the reaction mixture rising from 27 to 36 C. in about 5minutes. The reaction mixture was stirred for about 5 hours, filteredand the filter cake washed with water until the washings were neutral tolitmus. Upon drying the filter cake a tan colored solid, M. F. 68-72-C., was obtained in 83.7% yield. After recrystallization from diluteethyl alcohol the melting point was 7980 C. Analysis gave 6.44% nitrogenand 28.40% sulfur as compared to 6.16% nitrogen and 28.21% sulfurcalculated for C9H9NO2S2.

EXAMPLE 10 4-methyl-2- (Z-propynylmercapto)-5-thiaz0lyl methyl ketone -Asolution of 2-mercapto-4-methyl-5-thiazolyl methyl 5 period of 5minutes. The reaction mixture was stirred for about 5 hours, filtered,and the filter cake washed with water until the washings were neutral tolitmus. Upon drying the filter cake a tan colored product melting at6264 C. was obtained in 91% yield. After recrystallization from diluteethyl alcohol, the melting point was 65-66 C. Analysis gave 6.62%nitrogen and 30.29% sulfur as compared to 6.63% nitrogen and 30.35%sulfur calculated for C9H9NOS2.

A solution of 2-mercaptobenzoxazole was prepared by mixing 75.6 grams(0.5 mole) of 2-mercaptobenzoxazole, 500 grams of water and grams (0.5mole) of 25% aqueous sodium hydroxide. To the solution so prepared wasadded 59.5 grams (0.5 mole) of propargyl bromide. An exothermic reactionset in, the temperature of the reaction mixture rising from 28 to 35 C.over a 20 minute period. The reaction mixture was stirred for about 8hours, filtered and the filter cake washed with water until the washingswere neutral to litmus. Upon air drying the filter cake at 25 C., theproduct was obtained in 95% yield. After recrystallization from diluteethyl alcohol it melted at 51 C. Analysis gave 7.57% nitrogen and 16.95%sulfur as compared to 7.40% nitrogen and 16.95 sulfur calculated forCroHqNOS.

EXAMPLE 12 2- (Z-propynoxy -benzothiazole A solution of hydroxybenzothiazole was prepared by mixing 75.6 grams (0.5 mole) of hydroxybenzothiazole, 80 grams (0.5 mole) of 25% aqueous sodium hydroxide and500 grams of water. To the solution so prepared was added 59.5 grams(0.5 mole) of propargyl bromide. An exothermic reaction set in, thetemperature rising from 26 C. to 31 C. within. one hour. The reactionmixture was stirred for about 20 hours, extracted with 500 ml. of ether,the other layer washed with water until neutral, and dried over sodiumsulfate. The ether was removed in vacuo. The solid which resulted had amelting point of 76-78" C. Analysis gave 7.80% nitrogen and 17.35%sulfur as compared to 7.40% nitrogen and 16.95% sulfur calculated forC10H7NOS.

EXAMPLE 13 2,2-(Z-butynylenedimercapto) bisbenzothiazole A solution ofsodium Z-mercaptobenzothiazole was prepared by mixing 86 grams (0.5mole) of 97% mercaptobenzothiazole, 32.2 grams (0.5 mole) of 87%potassium hydroxide and 500 grams of ethyl alcohol. The resultingsolution was filtered to remove any insolubles and to the filtrate therewas added dropwise over a half hour period 37.5 grams (0.25 mole) of1,4-dichloro- 2-butyne. An exothermic reaction set in, the temperaturerising from 25 C. to 50 C. The reaction mixture was stirred for 18 hoursand then poured into 1000 grams of cold water. After stirring for 15minutes the precipitate was filtered, washed with water until neutral tolitmus .and air-dried at 25 C. A tan colored solid melting at 170-174 C.was obtained in 96.5% yield. After recrystallization from benzene themelting point was 177-179 C. Analysis gave 7.08% nitrogen compared to7.28% calculated for C1sH12N2S4.

Other examples of the new compounds are -methyl- 2 (2propynylmercapto)benzothiazole, 6 methyl-2-(2-propynylmercapto)benzothiazole, 7 methyl 2 (2propyny-lmercapto)benzothiazole, 4,6dimethyl-2-(2propynylmercapto)benzothiazole,4-chloro-2-(2-propynylmercapto)benzothiazole, 5 chloro2-(2-propynylmercapto) benzoxazole, 6 chloro2-(2-propynylmercapto)-benzoxazole, 7-chloro-2 (2propynylmercapto)benzoxazole, 6-p'henyl-2-(Z-propynylmercapto)benzothiazole, 6 methoxy-2-(2-propynylmercapto)benzothiazole, 5 ethoxy 2-(2-propynylmercap-to) -benzoxazole, 5 -methoxy-2- 2-propynylmercapto)benzoxazole, 2 (2 propynylmercapto) naphthothiazole, 4,5dimeth-yl-2-(Z-propynylmercapto) thiazole,4-ethyl-2-(Z-propynylmercapto)thiazole,4-propyl-2-(Zpropynylmercapto)thiazole,4-butyl-2-(2-propynylmercapto)thiazole,butyl-4-methyl-2-(2-propynylmercapto)-5-thiazolecarboxylate and4-methyl-2-(2-propynylmercapto)-5-thiazolecarboxylate. In the case ofderivatives of aliphatic thiazoles it is preferred that at least onealkyl group is present and that the alkyl group is a short chain alkylgroup, as for example of one to four carbon atoms inclusive. Similarly,carboalkoxy groups in which the alkoxy group contains one to four carbonatoms inclusive are preferred. Furthermore, propargyl halides condensewith 2-mercapto-4,S-dihydrothiazoles forming, for example2-(2-propynylmercapto)44,5- dihydrothiazole.

The new compounds possess accelerating properties for the vulcanizationof rubber. They are preferably used in conjunction :with a secondaryaccelerator like diphenyl guanidine. For example, a rubber stock wascompounded comprising The stocks so compounded were cured in the usualmanner by heating in a press at 135 C. The modulus and tensileproperties of the cured products are set forth below:

TABLE 1 Modulus Cure of Elas- Tensile at Ultimate Stock Time in ticityin Break in Elongation,

Mins. lbs/in. at lbs/in. Percent Elongation of 700% 30 1, 816 2, 040 74630 1, 493 2, 633 800 C 30 1, 2, 280 825 A. 60 2, 630 3, 540 770 B 60 3,210 3, 810 775 O 60 2, 530 3, 580 780 The new compounds are alsovaluable defoliants. The foilage of bean plants was completely destroyedby uniformly applying thereto an aqueous spray containing as the activeingredient a 1% concentration of 2-(2-butynylrnercapto)benzothiazole. Inpre-emergence application at the rate of 25 pounds per acre:ethyl-4-methyl-2- (2-propynylmercapto)-5-thiazolecarboxylate and 2-(2-propynoxy)benzothiazole proved to be effective herbicides. Some of thecompounds are fungicides, as for example2-(2-prcpynylmercapto)benzoxazole.

It is intended to cover all changes and modification-s of the examplesof the invention herein chosen for purposes of disclosure which do notconstitute departures from the spirit and scope of the invention.

This application is a continuation-in-part of application Serial No.302,819, filed August 5, 1952, now abandoned, and application Serial No.384,327, filed October 5, 1953, now abandoned.

What is claimed is:

1. A compound of the structure [(T-Y)wCnH2n-(w+2)]z where T represents aradical containing the azole ring where X is selected from the groupconsisting of oxygen and sulfur attached at the 24position to Y in whichthe valences of the carbon atoms in the 4- and 5-position are satisfiedby a member of the group consisting of hydrogen, alkyl radicalscontaining less than 5 carbon atoms, carboalkoxy radicals containingless than 6 carbon atoms, acetyl and carboxy radicals and residues ofcarbocyclic radicals, said carbocyclic radicals containing less than 11carbon atoms and being selected from the group consisting ofunsubstituted ortho-arylene, chloro substituted ortho-arylene,hydrocarbon substituted ortho-arylene, alkozy substitutedortho-pheny-lenc, hydroxy substituted ortho-phenylene and unsubstitutedphenenyl radicals having two of the three valences on adjacent carbonatoms, Y is selected from the group consisting of oxygen and sulfur,CnH2n(w+2) represents a radical derived from an alkyne hydrocarbon byremoval of at least one but less than three'hyd'rogen atoms, having thetriple bond in the beta position, w and z are integers at least 1 but.less than 3 and n is an integer at least 3 but not'more than 8.

2. The method which comprises reacting a halide of the structureCnH21r(w+2)Xw where X represents halogen and CnH2n(w+2) represents aradical derived from where M represents an alkali metal and X and Y areselected from the group consisting of oxygen and sulfur in which thevalences of the carbon atoms in the 4- and 5-position are satisfied by amember of the group consisting of hydrogen, alkyl radicals containingless than 5 carbon atoms, carboalkoxy radicals containing less than 6carbon atoms, acetyl and carboxy radicals and residues of carbocyclicradicals, said carbocyclic radicals containing less than 11 carbon atomand being selected from the group consisting of unsubstitutedortho-arylene, chloro substituted ortho-arylene, hydrocarbon substitutedortho-arylene, alkoxy substituted ortho-phenylene, hydroxy substitutedortho-phenylene and unsubstituted phenenyl radicals having two of thethree valances on adjacent carbon atoms.

3. A compound of the structure T--SCH2R where T represents a radicalcontaining the metathiazole ring attached at the 2-position to thesulfur atom in which the valences of the carbon atoms in the 4- and5-positions are satisfied by the residue of an unsubstitutedortho-phenylene group and R represents a radical derived from an alkynehydrocarbon group having less than 8 carbon atoms by removing onehydrogen atom and having the triple bond on the carbon next to the CH2group.

4. A compound of the structure H CSCH2Rr HOS/ where R represents analkyl group of less than 6 carbon atoms and R1 represents a radicalderived from an alkyne hydrocarbon group having less than 8 carbon atomsby removing one hydrogen atom and having the triple bond on the carbonnext to the CH2 group.

5. A compound of the structure where R and R2 represent alkyl groupscontaining less than 5 carbon atoms and R1 represents a radical derivedfrom an alkyne hydrocarbon group having less than 8 carbon atoms byremoving one hydrogen atom and having the triple bond on the carbon nextto the CH2 group.

6. A compound of the structure where R represents a lower alkyl radical.

7. A compound of the structure 8. A compound of the structure 9. Acompound of the structure 10.5-chloro-2-(2-propynylmercapto)benzothiazole.

11. 6-ethoxy-2-(2-propynylmercapto)benzothiazole.

12. The method which comprises reacting a halide of the structureCnH2n-3X where X represents halogen and CnH21r a represents a radicalderived from an alkyne hydrocarbon in which the triple bond is in thebeta position and n represents an integer at least 3 but not more than8, with an alkali metal salt of a Z-mercaptothiazole containing lessthan 14 carbon atoms and having a metathiazole ring attached to thesulfur atom in the 2-position .in which the valencesvof the carbon atomsin the 4- and S-positions are satisfied by a member of the groupconsisting of hydrogen, alkyl radicals containing less than 5 carbonatoms, carboalkoxy radicals containing less than 6 carbon atoms, acetyland carboxy radicals and residues of carbocyclic radicals, saidcarbocyclic radicals containing less than 11 carbon atoms and beingselected from the group consisting of unsubstituted ortho-arylene,chlo'ro substituted ortho-arylene, alkoxy substituted ortho-phenyleneand unsubstituted phenenyl radicals having two of the valances onadjacent carbon atoms in the thiazole 'ring and the third satisfied by asecond phenenyl group also part of a thiazole ring.

13. The method of claim 12 wherein the halide is propargyl chloride.

14. The method which comprises reacting the sodium salt of a Z-mercaptoarylene hydrocarbon thiazole con taining less than 12 carbon atoms witha halide of the structure ClCH2-R wherein R represents a radical derivedfrom an alkyne hydrocarbon group having less than 8 carbon atoms byremoving one hydrogen atom and having the triple bond on the carbon nextto the CH2 group.

15. The method which comprises reacting sodium mercaptobenzothiazolewith propargyl chloride in aqueous medium.

16. The method which comprises reacting sodium mer- "captobenzothiazolewith 'y-methyl propargyl chloride in aqueous medium.

17. The method which comprises reacting the sodium salt of a2-mercapto-4-alkyl thiazole of the structurewhere A represents an alkylgroup containing less than 5 carbon atoms with a halide of the structureClCHzR wherein R represents a radical derived from an alkyne hydrocarbongroup having less than 8 carbon atoms by removing one hydrogen atom andhaving the triple bond on the carbon next to the CH2 group.

18. The method which comprises reacting the sodium salt of2-mercapto-4-alkyl-5-carboalkoxythiazole in which the alkyl group andalkoxy group each contain less than 5 carbon atoms with propargylchloride in aqueous medium.

19. The method which comprises reacting propargyl chloride with thesodium salt of 2-mercapto-4-methyl-5- carbethoxythiazole in aqueousmedium, 1

No references cited.

1. A COMPOUND OF THE STRUCTURE